Abstract: The aim of this work was to study the safety and effectiveness of silver foam dressing (Contreet® Ag, Coloplast, Humlebaek, Denmark) in promoting the healing of infected venous ulcers over 9 weeks of treatment. Forty-two patients with infected venous ulcers were included and randomized into two groups. Group A had 21 patients (12 women and 9 men, mean age 61.2 years) who were treated with the silver foam for 9 weeks. Group B also had 21 patients (14 women and 7 men, mean age 58.7 years) who were treated with a nonadhesive foam (Biatain®, Coloplast, Humlebaek, Denmark) for 9 weeks. In both groups, ulcer size and depth, intensity of pain, wound exudation, bacterial load, side effects of both materials, and ulcer healing were documented and compared. There was no significant difference at the initial assessment in both groups regarding ulcer size, ulcer depth, grade of exudation, pain intensity, or bacterial load. However, group A ulcers had a significantly greater healing (P = 0.02) compared to group B. Pain intensity was significantly less in group A patients at several time points. After 9 weeks of treatment, the silver foam dressing was found to be a safe material that promotes rapid healing of venous ulcers and relieves pain.

Address correspondence to: Evangelos P. Dimakakos, MD, PhD, EFA/VM, MLD/CDT(P) Vascular Unit, 2nd Surgical Clinic Aretaieion University Hospital of Athens Aisopou 10 Maroussi Greece E-mail: edimakakos@yahoo.gr
     Venous ulcers are a significant problem for patients and the health system. Chronic venous insufficiency has many causes such as obesity, pregnancy, family history, and occupation.1,2 A patient with an ulcer usually suffers from bleeding, pain, and local or systemic infection. This chronic condition places a severe financial, social, and psychological burden on the patient and his or her family. 3 Wounds such as this must be treated quickly in an attempt to promote faster healing and prompt symptomatic relief. 4 Among the various materials that have been used to promote wound healing, the nonadhesive Contreet® Ag foam (Coloplast, Humlebaek, Denmark) appears to be one of the most promising. 5–8 This silver foam has a wide antimicrobial spectrum due to its silver properties and has had good healing results. 7,9,10      The aim of this study was to compare the effectiveness of nonadhesive, silver-releasing foam (Contreet Ag) versus nonadhesive foam (Biatain) in promoting healing of venous ulcers after 9 weeks of continuous treatment.

Methods

     The study protocol was approved by the Ethical Committee of Areteion University Hospital, Athens. All patients gave written informed consent.      During a 12-month period, all patients who had leg ulcers that were classified as exclusively infected and venous in origin were considered for inclusion in the study. All patients underwent baseline color Duplex study of their leg arteries and veins. Moreover, all infected venous ulcers had clinical signs of inflammation.      Exclusion criteria were: pregnancy, psychiatric disorders, diabetes, collagen disease, steroid use, history of allergies, or ankle-brachial pressure index (ABPI) < 1.      Ulcer healing after 9 weeks of treatment was the primary outcome measure of the study. The secondary end-point was the evolution of pain intensity. Forty-two patients were included in the study and were randomized into two groups: group A (21 patients; 12 women and 9 men, mean age 61.2 years), and group B (21 patients; 14 women and 7 men, mean age 58.7 years). In both groups, the initial wound diameter and depth was measured and the degree of exudation was evaluated. Wound pain was evaluated using a visual analogue scale (VAS) where 0 represented “no pain” and 10 represented the “worst imaginable pain.” Pain was categorized as mild (VAS score < 4), moderate (4–7), and severe (> 7). The degree of exudation was assessed by the amount of fluid on the dressing and was categorized as either mild (stain on the dressing), moderate and severe (fluid leakage from the dressing edges).      Following initial assessment, wounds were cleansed using sterile water and a 10% povidone iodine solution (Betadine, Lavipharm Hellas, Greece). Group A wounds were then covered with a nonadhesive silver-releasing foam measuring either 10 cm x 10 cm or 15 cm x 15 cm, depending on ulcer size. The same nurse wrapped the leg with a short stretch bandage, as compression therapy. In group B, wounds were covered with a nonadhesive foam measuring either 10 cm x 10 cm or 15 cm x 15 cm, depending on ulcer size. The leg was wrapped with a short stretch bandage, as compression therapy, by the same nurse.      Patients were followed for 9 weeks. Wound dressings were changed twice a week. Before each dressing change the intensity of pain was recorded, as previously described. Swab-cultures were obtained from every wound for bacterial load evaluation. Statistical analysis was performed using parametric and nonparametric tests as appropriate.

Results

     Twelve patients in group A and 14 patients in group B had a history of delayed ulcer healing (more than 1 month) before enrollment in this study.      In group A, initial ulcer diameter was < 1 cm in 2 patients; 1–2 cm in 5 patients; 2–3 cm in 4 patients; 3–4 cm in 7 patients; and > 4 cm in 3 patients (Table 1). Ulcer depth was < 0.5 cm in 14 patients and > 0.5 cm in 7 patients (Table 2). At initial assessment, 5 patients had severe pain, 11 had moderate pain, and 5 patients had mild or no pain (Table 3). At the same time, 6 patients had highly exuding ulcers, 11 had moderate exudation, and 4 had low exudation (Table 4).      In group B, the initial ulcer diameter was < 1 cm in 3 patients; 1–2 cm in 4 patients; 2–3 cm in 5 patients; 3–4 cm in 5 patients; and > 4 cm in 4 patients (Table 1). Ulcer depth was < 0.5 cm in 16 patients and > 0.5 cm in 5 patients (Table 2). Moreover, 5 patients had severe pain, 8 had moderate pain, and 8 patients had mild or no pain (Table 3). Finally, initial assessment of group B patients found that 8 had highly exuding ulcers, 8 had moderate exudation, and 5 patients had low exudation (Table 4). At the initial assessment, there was no statistically significant difference between the two groups regarding intensity of pain (P = 0.17; 95% CI [t-test]), degree of exudation, ulcer size (group A mean: 2.37; group B mean: 2.23), or ulcer depth (P = 0.74; 95% CI [χ2 test]).      After 9 weeks of treatment the healing rate was 81% in group A (17 of 21 patients) and 48% in group B (10 of 21 patients). The difference in the wound-healing rate between the two groups was statistically significant (P = 0.02; 95% CI [χ2 test]). Time to complete healing for both groups is shown in Table 5.      In group A, 57% (4 cases) of the deep ulcers (> 0.5 cm) and 93% (13 cases) of the more shallow ulcers (< 0.5 cm) healed by the end of 9 weeks of treatment. In group B during the same period, only 20% (1 case) of a deep ulcer and 56% (9 cases) of shallow ulcers achieved complete healing (Tables 6, 7). Additionally, 6 highly exuding ulcers, 10 ulcers with moderate exudation, and 1 ulcer with low exudation in group A had healed after 9 weeks of treatment, whereas in group B completed healing was not achieved in any patient with a highly exuding ulcer, but successful healing was achieved in 6 ulcers with moderate exudation and in 4 with low exudation.      Most of the patients in group A who had severe (2 of 5 patients) or moderate pain (8 of 11 patients) were pain-free by the end of the third week of treatment. All patients in group A (100%) were pain-free by the end of the eighth week of treatment. On the contrary, in group B, it took 4 weeks of treatment for the first patients with severe (1 of 5 patients) and moderate pain (3 of 8 patients) to be relieved from this symptom, while moderate pain persisted in 4 patients until the end of the 9-week treatment period. In group B, 13 patients (62%) were pain-free by the end of the ninth week of treatment.      Data on the bacterial load of the ulcers according to initial ulcer cultures is presented in Table 8 and Figure 1. There was no significant difference between groups regarding bacterial load. All patients with positive cultures were treated with appropriate antibiotics.      During the 9-week follow up period, none of the patients experienced systematic or local side effects that could be attributed to the use of the nonadhesive, silver-releasing foam or the nonadhesive foam.

Discussion

     Few clinical studies have shown a beneficial effect from the application of nonadhesive, silver-releasing foam (Contreet Ag) on ulcers with moderate to high exudation. However, the follow-up period in these studies is limited (up to 4 weeks).7,9,11–13 The present study is the first to address the issue of the effectiveness of a 9-week treatment with nonadhesive, silver-releasing foam in cases of infected venous ulcers that were unselected in terms of size and depth, degree of exudation, and history of delayed healing. The nonadhesive, silver-releasing foam was compared to a nonadhesive foam (Biatain), which was introduced in 1998 and quickly became popular due to its superior exudate management properties. This foam has a soft, skin-friendly adherent layer comprising less than 50% of the foam surface in order to maintain effective exudation management.14,15      A remarkable 81% of patients in group A compared to only 48% of patients in group B experienced complete ulcer healing within 9 weeks of treatment. Only 4 patients in group A required treatment for more than 9 weeks, most likely due to the history of delayed ulcer healing and not the grade of ulcer exudation, which was low in 1 patient, moderate in 2 patients, and high in 1 patient. It is known that the nonadhesive, silver-releasing foam is efficient in ulcers with high grade of exudation because of its absorptive capacity.10,11 Moreover, the nonadhesive, silver-releasing foam’s silver ions have a wide antibacterial spectrum that includes aerobes, anaerobes, multiresistant microorganisms, and fungi.5,10,12,16–18 Silver clears the wound of these microorganisms and accelerates the healing process.      Overall, the difference between the two groups was a factor of the optimal exudate management and the wide antibacterial spectrum of the nonadhesive, silver-releasing foam, a combination that promotes quick healing, and consequently, a decrease or resolution of ulcer-related pain.19 Finally, the lack of side effects of nonadhesive, silver-releasing foam in this study makes its use even more appealing.

Conclusion

     Despite recent advances in wound care, venous ulcers continue to be a challenging problem both for patients and the public health. Aside from medical complications that require costly treatment, chronic venous ulcers can also seriously affect quality of life for a patient and their family.20      This study is one of the first clinical studies to show that high rates of complete ulcer healing and pain resolution can be achieved in a reasonable amount of time (9 weeks) using a simple approach of topical wound care using a nonadhesive, silver-releasing foam. Particularly promising results were obtained in the “difficult” subgroup of patients, (ie, those with wide, deep, infected ulcers with a high degree of exudation).      Major limitations of the study include the small number of subjects and the difference of utilized materials. More detailed microbiological studies are needed to determine whether the known antibacterial effect of silver was a critical factor in the observed acceleration of healing. Larger clinical trials are necessary to determine optimal treatment protocols (duration, frequency of dressing changes, possible co-administration of other agents, etc.) for each subgroup of patients.